There is a well-recognized need for improved diagnostic methods for human filariasis. Clinical examination and microfilaria detection are insensitive, and serologic tests based on measurement of antifilarial antibodies have shown poor specificity. Our laboratory has been involved in studies of circulating filarial antigens (primarily in canine dirofilariasis) for the past two years. We developed a monoclonal antibody-based ELISA to detect circulating Dirofilaria immitis antigens and evaluated it with an extensive panel of well-characterized dog sera. Antigen detection was more sensitive and specific than microfilarial tests or antibody assays, and it provided an estimate of infection intensity not previously available for any filarial infection. Two D. immitis antigens were identified in infected dog sera by rocket-line electrophoresis. These antigens have been partially purified, and they appear to be acidic proteoglycans associated with the uterus and eggs in adult female worms. We now plan to perform similiar studies of circulating parasite antigens in human filariasis. Preliminary studies have indicated that parasite antigens are detectable by counterimmunoelectrophoresis in the serum and urine of patients infected with W. bancrofti. We will develop sensitive monoclonal antibody-based assays for circulating antigens of W. bancrofti and Brugia malayi with techniques used in our D. immitis study. We will also identify and characterize circulating filarial antigens and study their immunogenicity in the human host. Filarial antigen assays will be systematically evaluated as clinical and epidemiological tools in collaboration with the Indian National Intitute of Communicable Diseases which has extensive ongoing studies of filariasis epidemiology in Kerala (endemic for W. bancrofti and B. malayi). This evaluation will include studies of the distribution of infection intensities in populations, the age at acquisition of infection, the possible influence of the infection status of the mother on susceptibility to infection in offspring, and the use of parasite antigen detection to monitor filariasis treatment.